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PMID: 25085911 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Endocytosis, signaling, and beyond.

Cold Spring Harbor perspectives in biology ·Vol. 6 ·No. 8 ·2014-08-01

Di Fiore PP, von Zastrow M

Abstract

The endocytic network comprises a vast and intricate system of membrane-delimited cell entry and cargo sorting routes running between biochemically and functionally distinct intracellular compartments. The endocytic network caters to the organization and redistribution of diverse subcellular components, and mediates appropriate shuttling and processing of materials acquired from neighboring cells or the extracellular milieu. Such trafficking logistics, despite their importance, represent only one facet of endocytic function. The endocytic network also plays a key role in organizing, mediating, and regulating cellular signal transduction events. Conversely, cellular signaling processes tightly control the endocytic pathway at different steps. The present article provides a perspective on the intimate relationships that exist between particular endocytic and cellular signaling processes in mammalian cells, within the context of understanding the impact of this nexus on integrated physiology.

MeSH Terms
Endocytosis/physiology Endosomes/metabolism,physiology Gene Expression Regulation Metabolic Networks and Pathways Models, Biological Protein Transport Signal Transduction Transcription, Genetic
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Di Fiore Pier Paolo
Department of Experimental Oncology, Istituto Europeo di Oncologia, 20141 Milan, Italy Dipartimento di Scienze della Salute, Università degli Studi di Milano, 20122 Milan, Italy.
von Zastrow Mark
Department of Psychiatry, University of California San Francisco School of Medicine, San Francisco, California 94158 Department of Cellular & Molecular Pharmacology, University of California San Francisco School of Medicine, San Francisco, California 94158.
References (108)
108 references, click to expand
  1. Regulation of postsynaptic retrograde signaling by presynaptic exosome release.
    Neuron. 2013 Mar 20;77(6):1039-46 PMID: 23522040
  2. Membrane shaping by the Bin/amphiphysin/Rvs (BAR) domain protein superfamily.
    Cell Mol Life Sci. 2011 Dec;68(24):3983-93 PMID: 21769645
  3. Rab proteins and the compartmentalization of the endosomal system.
    Cold Spring Harb Perspect Biol. 2014 Oct 23;6(11):a022616 PMID: 25341920
  4. A unique platform for H-Ras signaling involving clathrin-independent endocytosis.
    Mol Biol Cell. 2008 Mar;19(3):765-75 PMID: 18094044
  5. Wingless secretion promotes and requires retromer-dependent cycling of Wntless.
    Nat Cell Biol. 2008 Feb;10(2):178-85 PMID: 18193032
  6. Regulation of endocytosis via the oxygen-sensing pathway.
    Nat Med. 2009 Mar;15(3):319-24 PMID: 19252501
  7. The endocytic matrix.
    Nature. 2010 Jan 28;463(7280):464-73 PMID: 20110990
  8. C. elegans AP-2 and retromer control Wnt signaling by regulating mig-14/Wntless.
    Dev Cell. 2008 Jan;14(1):132-9 PMID: 18160346
  9. Requirements for F-BAR proteins TOCA-1 and TOCA-2 in actin dynamics and membrane trafficking during Caenorhabditis elegans oocyte growth and embryonic epidermal morphogenesis.
    PLoS Genet. 2009 Oct;5(10):e1000675 PMID: 19798448
  10. Molecular mechanisms of the membrane sculpting ESCRT pathway.
    Cold Spring Harb Perspect Biol. 2013 Sep 01;5(9): PMID: 24003212
  11. Coordination between RAB GTPase and phosphoinositide regulation and functions.
    Nat Rev Mol Cell Biol. 2012 Jun 22;13(7):463-70 PMID: 22722608
  12. The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network.
    Dev Cell. 2008 Jan;14(1):120-31 PMID: 18160348
  13. A gene network regulating lysosomal biogenesis and function.
    Science. 2009 Jul 24;325(5939):473-7 PMID: 19556463
  14. Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic.
    Nat Cell Biol. 2007 Sep;9(9):1066-73 PMID: 17704769
  15. Molecular mechanism and physiological functions of clathrin-mediated endocytosis.
    Nat Rev Mol Cell Biol. 2011 Jul 22;12(8):517-33 PMID: 21779028
  16. A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes.
    Cell. 2009 Mar 20;136(6):1110-21 PMID: 19303853
  17. Internalization of D1 dopamine receptor in striatal neurons in vivo as evidence of activation by dopamine agonists.
    J Neurosci. 1998 Mar 1;18(5):1650-61 PMID: 9464990
  18. Secretion of Wnt ligands requires Evi, a conserved transmembrane protein.
    Cell. 2006 May 5;125(3):523-33 PMID: 16678096
  19. SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane.
    J Cell Biol. 2010 Aug 23;190(4):565-74 PMID: 20733053
  20. Role of AMPA receptor cycling in synaptic transmission and plasticity.
    Neuron. 1999 Nov;24(3):649-58 PMID: 10595516
  21. Cell biology: Receptor signals come in waves.
    Nature. 2013 Mar 28;495(7442):457-8 PMID: 23515157
  22. Autophagy in lysosomal storage disorders.
    Autophagy. 2012 May 1;8(5):719-30 PMID: 22647656
  23. EGF stimulates annexin 1-dependent inward vesiculation in a multivesicular endosome subpopulation.
    EMBO J. 2006 Jan 11;25(1):1-12 PMID: 16052208
  24. Exosomes go with the Wnt.
    Cell Logist. 2012 Jul 1;2(3):169-173 PMID: 23739155
  25. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases.
    Cancer Res. 1999 Nov 15;59(22):5830-5 PMID: 10582706
  26. Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes.
    Cell. 2010 Dec 23;143(7):1136-48 PMID: 21183076
  27. Rab5 is necessary for the biogenesis of the endolysosomal system in vivo.
    Nature. 2012 May 23;485(7399):465-70 PMID: 22622570
  28. Synaptic AMPA receptor plasticity and behavior.
    Neuron. 2009 Feb 12;61(3):340-50 PMID: 19217372
  29. Recycling endosomes in apical plasma membrane domain formation and epithelial cell polarity.
    Trends Cell Biol. 2010 Oct;20(10):618-26 PMID: 20833047
  30. Wnt trafficking: new insights into Wnt maturation, secretion and spreading.
    Traffic. 2010 Oct;11(10):1265-71 PMID: 20477987
  31. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop.
    Nat Cell Biol. 2013 Jun;15(6):647-58 PMID: 23604321
  32. Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation.
    Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18598-603 PMID: 19841259
  33. Caenorhabditis elegans screen reveals role of PAR-5 in RAB-11-recycling endosome positioning and apicobasal cell polarity.
    Nat Cell Biol. 2012 May 27;14(7):666-76 PMID: 22634595
  34. Recovery from mu-opioid receptor desensitization after chronic treatment with morphine and methadone.
    J Neurosci. 2011 Mar 23;31(12):4434-43 PMID: 21430144
  35. Cargo sorting in the endocytic pathway: a key regulator of cell polarity and tissue dynamics.
    Cold Spring Harb Perspect Biol. 2014 Aug 14;6(10):a016899 PMID: 25125399
  36. RAB-5 controls the cortical organization and dynamics of PAR proteins to maintain C. elegans early embryonic polarity.
    PLoS One. 2012;7(4):e35286 PMID: 22545101
  37. Sprinter: a novel transmembrane protein required for Wg secretion and signaling.
    Development. 2006 Dec;133(24):4901-11 PMID: 17108000
  38. Regulation of endocytic clathrin dynamics by cargo ubiquitination.
    Dev Cell. 2012 Sep 11;23(3):519-32 PMID: 22940114
  39. Endocytosis and signaling: cell logistics shape the eukaryotic cell plan.
    Physiol Rev. 2012 Jan;92(1):273-366 PMID: 22298658
  40. Kinetics of morphogen gradient formation.
    Science. 2007 Jan 26;315(5811):521-5 PMID: 17255514
  41. A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport.
    Nat Cell Biol. 2013 May;15(5):461-71 PMID: 23563491
  42. Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways.
    Hum Mol Genet. 2011 Oct 1;20(19):3852-66 PMID: 21752829
  43. Regulation of developmental intercellular signalling by intracellular trafficking.
    EMBO J. 2011 Aug 31;30(17):3516-26 PMID: 21878993
  44. Xenopus Wntless and the retromer complex cooperate to regulate XWnt4 secretion.
    Mol Cell Biol. 2009 Apr;29(8):2118-28 PMID: 19223472
  45. mu-Opioid receptor internalization: opiate drugs have differential effects on a conserved endocytic mechanism in vitro and in the mammalian brain.
    Mol Pharmacol. 1998 Mar;53(3):377-84 PMID: 9495801
  46. Wnt/beta-catenin pathway.
    Sci STKE. 2005 Feb 15;2005(271):cm1 PMID: 15713948
  47. Systems survey of endocytosis by multiparametric image analysis.
    Nature. 2010 Mar 11;464(7286):243-9 PMID: 20190736
  48. Transport at the recycling endosome.
    Curr Opin Cell Biol. 2010 Aug;22(4):528-34 PMID: 20541925
  49. A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion.
    Nat Cell Biol. 2011 Jul 03;13(8):914-923 PMID: 21725319
  50. Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells.
    Dev Cell. 2008 Jan;14(1):140-7 PMID: 18160347
  51. Function and regulation of the endosomal fusion and fission machineries.
    Cold Spring Harb Perspect Biol. 2014 Mar 01;6(3): PMID: 24591520
  52. Lysosomal adaptation: how the lysosome responds to external cues.
    Cold Spring Harb Perspect Biol. 2014 May 05;6(6): PMID: 24799353
  53. Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis.
    Nature. 2005 Jul 7;436(7047):78-86 PMID: 15889048
  54. Dynamin participates in the maintenance of anterior polarity in the Caenorhabditis elegans embryo.
    Dev Cell. 2009 Jun;16(6):889-900 PMID: 19531359
  55. Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex.
    Nat Cell Biol. 2008 Feb;10(2):170-7 PMID: 18193037
  56. The early endosome: a busy sorting station for proteins at the crossroads.
    Histol Histopathol. 2010 Jan;25(1):99-112 PMID: 19924646
  57. Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells.
    Cell. 2006 May 5;125(3):509-22 PMID: 16678095
  58. Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin).
    Mol Biol Cell. 2012 Dec;23(23):4623-34 PMID: 23051738
  59. Single-cell analysis of population context advances RNAi screening at multiple levels.
    Mol Syst Biol. 2012 Apr 24;8:579 PMID: 22531119
  60. Rab conversion as a mechanism of progression from early to late endosomes.
    Cell. 2005 Sep 9;122(5):735-49 PMID: 16143105
  61. Reconstitution of Rab- and SNARE-dependent membrane fusion by synthetic endosomes.
    Nature. 2009 Jun 25;459(7250):1091-7 PMID: 19458617
  62. The regulation of the endosomal compartment by p53 the tumor suppressor gene.
    FEBS J. 2009 Apr;276(8):2201-12 PMID: 19302216
  63. Mutant p53 drives invasion by promoting integrin recycling.
    Cell. 2009 Dec 24;139(7):1327-41 PMID: 20064378
  64. Interpretation of the FGF8 morphogen gradient is regulated by endocytic trafficking.
    Nat Cell Biol. 2011 Feb;13(2):153-8 PMID: 21258372
  65. Neuronal signaling through endocytosis.
    Cold Spring Harb Perspect Biol. 2014 Feb 01;6(2): PMID: 24492712
  66. Wnt signaling: a common theme in animal development.
    Genes Dev. 1997 Dec 15;11(24):3286-305 PMID: 9407023
  67. Clathrin-independent pathways of endocytosis.
    Cold Spring Harb Perspect Biol. 2014 Jun 02;6(6): PMID: 24890511
  68. SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors.
    Nat Cell Biol. 2011 Jun;13(6):715-21 PMID: 21602791
  69. Wnt/β-catenin signaling and disease.
    Cell. 2012 Jun 8;149(6):1192-205 PMID: 22682243
  70. Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless.
    Cell. 2009 Oct 16;139(2):393-404 PMID: 19837038
  71. Molecules, mechanisms, and cellular roles of clathrin-independent endocytosis.
    Curr Opin Cell Biol. 2010 Aug;22(4):519-27 PMID: 20439156
  72. In vivo delta opioid receptor internalization controls behavioral effects of agonists.
    PLoS One. 2009;4(5):e5425 PMID: 19412545
  73. On the fate of early endosomes.
    Biol Chem. 2009 Aug;390(8):753-9 PMID: 19361275
  74. Presynaptic membrane retrieval and endosome biology: defining molecularly heterogeneous synaptic vesicles.
    Cold Spring Harb Perspect Biol. 2013 Oct 01;5(10):a016915 PMID: 24086045
  75. Identification of the switch in early-to-late endosome transition.
    Cell. 2010 Apr 30;141(3):497-508 PMID: 20434987
  76. RNAi screening reveals proteasome- and Cullin3-dependent stages in vaccinia virus infection.
    Cell Rep. 2012 Oct 25;2(4):1036-47 PMID: 23084750
  77. Clathrin is a key regulator of basolateral polarity.
    Nature. 2008 Apr 10;452(7188):719-23 PMID: 18401403
  78. Regulation of cardiac contractility by Rab4-modulated beta2-adrenergic receptor recycling.
    Proc Natl Acad Sci U S A. 2004 May 4;101(18):7082-7 PMID: 15105445
  79. Clathrin-independent endocytosis: mechanisms and function.
    Curr Opin Cell Biol. 2011 Aug;23(4):413-20 PMID: 21466956
  80. Rab GTPases as coordinators of vesicle traffic.
    Nat Rev Mol Cell Biol. 2009 Aug;10(8):513-25 PMID: 19603039
  81. Endosome maturation.
    EMBO J. 2011 Aug 31;30(17):3481-500 PMID: 21878991
  82. Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis.
    Curr Biol. 2008 Nov 11;18(21):1639-48 PMID: 18976911
  83. Molecular structure, function, and dynamics of clathrin-mediated membrane traffic.
    Cold Spring Harb Perspect Biol. 2014 May 01;6(5):a016725 PMID: 24789820
  84. Rab proteins as membrane organizers.
    Nat Rev Mol Cell Biol. 2001 Feb;2(2):107-17 PMID: 11252952
  85. The PDZ-binding motif of the beta2-adrenoceptor is essential for physiologic signaling and trafficking in cardiac myocytes.
    Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10776-81 PMID: 12954981
  86. Sequence-dependent sorting of recycling proteins by actin-stabilized endosomal microdomains.
    Cell. 2010 Nov 24;143(5):761-73 PMID: 21111236
  87. Lipid sorting and multivesicular endosome biogenesis.
    Cold Spring Harb Perspect Biol. 2013 Oct 01;5(10):a016816 PMID: 24086044
  88. TFEB links autophagy to lysosomal biogenesis.
    Science. 2011 Jun 17;332(6036):1429-33 PMID: 21617040
  89. Agonist-selective endocytosis of mu opioid receptor by neurons in vivo.
    Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9241-6 PMID: 8799185
  90. A dedicated Wnt secretion factor.
    Cell. 2006 May 5;125(3):432-3 PMID: 16678089
  91. Endocytosis and signalling: intertwining molecular networks.
    Nat Rev Mol Cell Biol. 2009 Sep;10(9):609-22 PMID: 19696798
  92. EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy.
    Nat Med. 2011 May;17(5):589-95 PMID: 21516087
  93. Internalization is required for proper Wingless signaling in Drosophila melanogaster.
    J Cell Biol. 2006 Apr 10;173(1):95-106 PMID: 16606693
  94. Retromer: a master conductor of endosome sorting.
    Cold Spring Harb Perspect Biol. 2014 Feb 01;6(2): PMID: 24492709
  95. Signals from the lysosome: a control centre for cellular clearance and energy metabolism.
    Nat Rev Mol Cell Biol. 2013 May;14(5):283-96 PMID: 23609508
  96. Polarity and endocytosis: reciprocal regulation.
    Trends Cell Biol. 2010 Aug;20(8):445-52 PMID: 20493706
  97. Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome.
    Nat Med. 2013 Apr;19(4):473-80 PMID: 23524343
  98. Ubiquitin-dependent sorting in endocytosis.
    Cold Spring Harb Perspect Biol. 2014 Jan 01;6(1): PMID: 24384571
  99. The role of endocytosis during morphogenetic signaling.
    Cold Spring Harb Perspect Biol. 2014 Jul 01;6(7):a016881 PMID: 24984777
  100. Endocytic accessory factors and regulation of clathrin-mediated endocytosis.
    Cold Spring Harb Perspect Biol. 2014 Oct 03;6(11):a016733 PMID: 25280766
  101. Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules.
    Nature. 2009 Sep 24;461(7263):533-6 PMID: 19741606
  102. Population context determines cell-to-cell variability in endocytosis and virus infection.
    Nature. 2009 Sep 24;461(7263):520-3 PMID: 19710653
  103. Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments.
    Cell. 1990 Jul 27;62(2):317-29 PMID: 2115402
  104. Cargo regulates clathrin-coated pit dynamics.
    Cell. 2006 Oct 6;127(1):113-24 PMID: 17018281
  105. Conformational biosensors reveal GPCR signalling from endosomes.
    Nature. 2013 Mar 28;495(7442):534-8 PMID: 23515162
  106. Multisubunit tethering complexes and their role in membrane fusion.
    Curr Biol. 2010 Nov 9;20(21):R943-52 PMID: 21056839
  107. Endocytosis promotes rapid dopaminergic signaling.
    Neuron. 2011 Jul 28;71(2):278-90 PMID: 21791287
  108. Caveolae as plasma membrane sensors, protectors and organizers.
    Nat Rev Mol Cell Biol. 2013 Feb;14(2):98-112 PMID: 23340574
Article Info
Journal
Cold Spring Harbor perspectives in biology
Abbr.
Cold Spring Harb Perspect Biol
ISSN
1943-0264
DOI
10.1101/cshperspect.a016865
Published
2014-08-01
Epub
2014-00-01
Language
English
Region
United States
NLM ID
101513680
PMCID
PMC4107983
Subset
IM
Grants
NIDA NIH HHS · P01 DA010154 · United States
NIDA NIH HHS · R01 DA010711 · United States
NIDA NIH HHS · R01 DA012864 · United States
External Links
PubMed source DOI: 10.1101/cshperspect.a016865 PMC Full Text View journal details
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